CD4+ Th1 to the rescue in HER-2+ breast cancer

HER2 overexpression leads to downregulation of MHC class-I. CD4⁺ Th1 cytokines, IFNγ and TNFα, and monoclonal antibodies, trastuzumab and pertuzumab, restore MHC class-I expression, and enable CD8⁺ recognition and cytolysis. Restoration of the anti-HER2 CD4⁺ Th1 immune response in combination with HER2 targeted therapy appear to be critical to successful anti-HER2 CD8⁺ immunotherapy.